mRNAs, proteins and the emerging principles of gene expression control

Nature Reviews Genetics, Journal Year: 2020, Volume and Issue: 21(10), P. 630 - 644

Published: July 24, 2020

Language: Английский

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Expansion sequencing: Spatially precise in situ transcriptomics in intact biological systems

Science, Journal Year: 2021, Volume and Issue: 371(6528)

Published: Jan. 28, 2021

Identifying transcript location in cells where specific RNAs occur within a cell or tissue has been limited by technology and imaging capabilities. Expansion microscopy allowed for better visualization of small structures expanding the tissues with polymer- hydrogel-based system. Alon et al. combined expansion long-read situ RNA sequencing, resulting more precise transcripts. This method, termed “ExSeq” was used to detect RNAs, both new transcripts those previously demonstrated localize neuronal dendrites. Unlike other sequencing methods, ExSeq does not target sets genes. thus unites spatial resolution, multiplexing, an unbiased approach reveal insights into localization its physiological roles developing active tissue. Science , this issue p. eaax2656

Language: Английский

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Intracellular mRNA transport and localized translation

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 22(7), P. 483 - 504

Published: April 9, 2021

Language: Английский

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Monosomes actively translate synaptic mRNAs in neuronal processes

Science, Journal Year: 2020, Volume and Issue: 367(6477)

Published: Jan. 31, 2020

To accommodate their complex morphology, neurons localize messenger RNAs (mRNAs) and ribosomes near synapses to produce proteins locally. However, a relative paucity of polysomes (considered the active sites translation) detected in electron micrographs neuronal processes has suggested limited capacity for local protein synthesis. In this study, we used polysome profiling together with ribosome footprinting microdissected rodent synaptic regions reveal surprisingly high number dendritic and/or axonal transcripts preferentially associated monosomes (single ribosomes). Furthermore, were process Most mRNAs showed similar translational status cell bodies neurites, but some exhibited differential occupancy compartments. Monosome-preferring often encoded high-abundance proteins. Thus, monosome translation contributes proteome.

Language: Английский

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Dendritic Spine Plasticity: Function and Mechanisms

Frontiers in Synaptic Neuroscience, Journal Year: 2020, Volume and Issue: 12

Published: Aug. 28, 2020

Dendritic spines are small protrusions studding neuronal dendrites, first described in 1888 by Ramón y Cajal using his famous Golgi stainings. Around fifty years later the advance of electron microscopy confirmed Cajal's intuition that constitute postsynaptic site most excitatory synapses mammalian brain. The finding spine density decreases between young and adult ages fixed tissues suggested dynamic. It is only a decade ago two-photon has unambiguously proven dynamic nature spines, through repeated imaging single live animals. Spine dynamics comprise formation, disappearance stabilization modulated activity developmental age. Here we review several emerging concepts field start to answer following key questions: What external signals triggering molecular mechanisms involved? is, return, role circuit rewiring, learning neuropsychiatric disorders?

Language: Английский

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The science of puromycin: From studies of ribosome function to applications in biotechnology

Computational and Structural Biotechnology Journal, Journal Year: 2020, Volume and Issue: 18, P. 1074 - 1083

Published: Jan. 1, 2020

Puromycin is a naturally occurring aminonucleoside antibiotic that inhibits protein synthesis by ribosome-catalyzed incorporation into the C-terminus of elongating nascent chains, blocking further extension and resulting in premature termination translation. It most commonly known as selection marker for cell lines genetically engineered to express resistance transgene, but its additional uses probe have proven invaluable across wide variety model systems, ranging from purified ribosomes cell-free translation intact cultured cells whole animals. comprised nucleoside covalently bound an amino acid, mimicking 3′ end aminoacylated tRNAs participate delivery acids ribosomes. Both moieties can tolerate some chemical substitutions modifications without significant loss activity, generating diverse toolbox puromycin-based reagents with added functionality, such biotin affinity purification or fluorophores fluorescent microscopy detection. These reagents, well anti-puromycin antibodies, played pivotal role advancing our understanding regulation dysregulation normal pathological processes, including immune response neurological function. This manuscript reviews current state research, structure mechanism action, relevant derivatives, use advanced methodologies major insights generated using techniques both lab clinic.

Language: Английский

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RNA transport and local translation in neurodevelopmental and neurodegenerative disease

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(5), P. 622 - 632

Published: Jan. 28, 2021

Language: Английский

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The translatome of neuronal cell bodies, dendrites, and axons

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(43)

Published: Oct. 20, 2021

Significance Proteins are the key drivers of neuronal synaptic function. The regulation gene expression is important for formation and modification synapses throughout lifespan. complexity dendrites axons imposes unique challenges protein supply at remote locations. discovery messenger RNAs (mRNAs) ribosomes near has shown that local synthesis represents an solution to this challenge. Here we used RNA sequencing ribosome determine directly population mRNAs present in process translation cell bodies, dendrites, axons. Thousands transcripts were differentially translated between body regions with over 800 exhibiting more dendritic–axonal compartment.

Language: Английский

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Neuronal ribosomes exhibit dynamic and context-dependent exchange of ribosomal proteins

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 21, 2021

Abstract Owing to their morphological complexity and dense network connections, neurons modify proteomes locally, using mRNAs ribosomes present in the neuropil (tissue enriched for dendrites axons). Although ribosome biogenesis largely takes place nucleus perinuclear region, neuronal ribosomal protein (RP) have been frequently detected remotely, axons. Here, imaging profiling, we directly RP translation neuropil. Combining brief metabolic labeling with mass spectrometry, found that a group of RPs rapidly associated translating cytoplasm this incorporation was independent canonical biogenesis. Moreover, probability some regulated by location (neurites vs. cell bodies) changes cellular environment (following oxidative stress). Our results suggest new mechanisms local activation, repair and/or specialization translational machinery within processes, potentially allowing synapses rapid means regulate synthesis.

Language: Английский

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Liquid-Liquid Phase Separation of TDP-43 and FUS in Physiology and Pathology of Neurodegenerative Diseases

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Feb. 2, 2022

Liquid-liquid phase separation of RNA-binding proteins mediates the formation numerous membraneless organelles with essential cellular function. However, aberrant transition these leads to insoluble protein aggregates, which are pathological hallmarks neurodegenerative diseases including ALS and FTD. TDP-43 FUS two such that mislocalize aggregate in patients They have similar domain structures provide multivalent interactions driving their vitro environment. In this article, we review factors mediate regulate FUS. We also evidences connect property functional roles cells. Aberrant aggregation disrupts regular cell Therefore, restoration could be beneficial for neuronal discuss possible mechanisms while reviewing methods currently being explored as potential therapeutic strategies mitigate

Language: Английский

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